坎替沙坦抑制大鼠去窦弓神经引起的心血管肥大

摘要

AIM: To study the effect of candesartan cilexetil (candesartan), a new AT1 receptor antagonist, on sinoaortic denervation (SAD)-induced cardiovascular hypertrophy and its potential mechanisms in rats. METHODS: For long-term treatment, candesartan (6 mg@kg-1@d-1) was given in rat food for 16 weeks after SAD surgery, and for acute treatment, a single dose of candesartan (3 mg/kg) was administrated intragastrically at 30 d after SAD.RESULTS: The indexes of left ventricular and aortic hypertrophy in candesartan-treated SAD rats were decreased when compared with untreated SAD rats, and similar to or less than those in normal rats. SAD-induced cardiomyocyte hypertrophy, myocardial fibrosis, wall thickening of intramyocardial arterioles and aortae, and destruction of vas cular internal elastin membrane were almost inhibited by candesartan. The plasma angiotensin II levels were markedly increased in treated SAD rats and negatively correlated with the indexes of hypertrophy. Both blood pressure and its variability were reduced by a single dose of candesartan during 3 h of observation period.CONCLUSION: Candesartan can efficiently inhibit SAD-induced cardiovascular hypertrophy. In addition to known mechanisms, upregulation of circulating angiotensin II and stabilization of blood pressure may be involved in this cardiovascular protection of candesartan.%目的:研究新型AT1受体拮抗剂坎替沙坦对大鼠去窦弓神经(SAD)引起的心血管肥大的作用及其可能机制.方法:长期治疗时,大鼠SAD术后从食物中给予坎替沙坦(6 mg.kg-1.d-1)16周.急性治疗时,大鼠SAD术后第30天经胃内单次给坎替沙坦3 mg/kg.结果:SAD大鼠坎替沙坦治疗组的左心室和主动脉肥厚指数明显低于未治疗组,相当于或低于正常水平.SAD引起的心肌肥大、纤维化、心肌内小动脉和主动脉管壁增厚以及血管内弹力膜破坏几乎被坎替沙坦完全抑制.治疗后血浆血管紧张素II浓度明显升高,与心血管肥厚指数呈负相关.坎替沙坦单次给药后3小时观察期内,SAD大鼠血压及其波动性维持在较低水平.结论:坎替沙坦能有效抑制SAD引起的心血管肥厚.这种心血管保护作用除与已知机制有关外,还可能与其上调循环血管紧张素II和稳定血压有关.